TY - JOUR
T1 - A phase IB/IL study of gemcitabine and docetaxel in combination with pazopanib for the neoadjuvant treatment of soft tissue sarcomas
AU - Munhoz, Rodrigo R.
AU - D’Angelo, Sandra P.
AU - Gounder, Mrinal M.
AU - Keohan, Mary L.
AU - Chi, Ping
AU - Carvajal, Richard D.
AU - Singer, Samuel
AU - Crago, Aimee M.
AU - Landa, Jonathan
AU - Healey, John H.
AU - Qin, Li Xuan
AU - Hameed, Meera
AU - Ezeoke, Mariettao
AU - Singh, Arun S.
AU - Agulnik, Mark
AU - Chmielowski, Bartosz
AU - Luke, Jason J.
AU - Vantine, Brian A.
AU - Schwartz, Gary K.
AU - Tap, William D.
AU - Dickson, Mark A.
N1 - Publisher Copyright:
© AlphaMed Press 2015.
PY - 2015/10/8
Y1 - 2015/10/8
N2 - Background. For extremity soft tissue sarcomas (STS), surgical resection remains the standard of care, and the addition of chemotherapy is controversial. This was a phase Ib/II trial of neoadjuvant therapy for patients with STS. Methods. Patients with high grade, extremity STS of >8cm and amenable to definitive resection were treated with up to four 21-day cycles of 900 mg/m2 gemcitabine on days 1 and 8, 75 mg/m2 docetaxel on day 8, and 400 mg of pazopanib daily (GDP), followed by surgery and, if indicated, radiation therapy. Primary and secondary endpoints (phase Ib portion) were the safety and rate of pathologic response. Results. The trial was discontinued because of slow accrual after inclusion of five patients (leiomyosarcoma: two; undifferentiated pleomorphic sarcoma: three). Two patients completed four treatment cycles: one underwent surgery and one had insufficient response and received additional therapies. Three patients discontinued treatment because of toxicity. Grade 3 adverse events included hypertension, fatigue, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, hoarseness, and myelotoxicity. There were no complete or partial responses. One patient had $90% pathologic response. Among four patients who underwent resection, three remain free of disease, and one patient eventually relapsed. Conclusion. GDP combination used in the neoadjuvant setting resulted in significanttoxicity; despite pathologic responses, no objective responses occurred.
AB - Background. For extremity soft tissue sarcomas (STS), surgical resection remains the standard of care, and the addition of chemotherapy is controversial. This was a phase Ib/II trial of neoadjuvant therapy for patients with STS. Methods. Patients with high grade, extremity STS of >8cm and amenable to definitive resection were treated with up to four 21-day cycles of 900 mg/m2 gemcitabine on days 1 and 8, 75 mg/m2 docetaxel on day 8, and 400 mg of pazopanib daily (GDP), followed by surgery and, if indicated, radiation therapy. Primary and secondary endpoints (phase Ib portion) were the safety and rate of pathologic response. Results. The trial was discontinued because of slow accrual after inclusion of five patients (leiomyosarcoma: two; undifferentiated pleomorphic sarcoma: three). Two patients completed four treatment cycles: one underwent surgery and one had insufficient response and received additional therapies. Three patients discontinued treatment because of toxicity. Grade 3 adverse events included hypertension, fatigue, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, hoarseness, and myelotoxicity. There were no complete or partial responses. One patient had $90% pathologic response. Among four patients who underwent resection, three remain free of disease, and one patient eventually relapsed. Conclusion. GDP combination used in the neoadjuvant setting resulted in significanttoxicity; despite pathologic responses, no objective responses occurred.
UR - http://www.scopus.com/inward/record.url?scp=84946553342&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2015-0245
DO - 10.1634/theoncologist.2015-0245
M3 - Article
C2 - 26449382
AN - SCOPUS:84946553342
SN - 1083-7159
VL - 20
SP - 1245
EP - 1246
JO - Oncologist
JF - Oncologist
IS - 11
ER -